SVMyr: A Web Server Detecting Co- and Post-translational Myristoylation in Proteins

Abstract

Myristoylation (MYR) is a protein modification where a myristoyl group is covalently attached to an exposed (N-terminal) glycine residue. Glycine myristoylation occurs during protein translation (co-translation) or after (post-translation). Myristoylated proteins have a role in signal transduction, apoptosis, and pathogen-mediated processes and their prediction can help in functionally annotating the fraction of proteins undergoing MYR in different proteomes. Here we present SVMyr, a web server allowing the detection of both co- and post-translational myristoylation sites, based on Support Vector Machines (SVM). The input encodes composition and physicochemical features of the octapeptides, known to act as substrates and to physically interact with N-myristoyltransferases (NMTs), the enzymes catalyzing the myristoylation reaction. The method, adopting a cross validation procedure, scores with values of Area Under the Curve (AUC) and Matthews Correlation Coefficient (MCC) of 0.92 and 0.61, respectively. When benchmarked on an independent dataset including experimentally detected 88 medium/high confidence co-translational myristoylation sites and 528 negative examples, SVMyr outperforms available methods, with AUC and MCC equal to 0.91 and 0.58, respectively. A unique feature of SVMyr is the ability to predict post-translational myristoylation sites by coupling the trained SVMs with the detection of caspase cleavage sites, identified by searching regular motifs matching upstream caspase cleavage sites, as reported in literature. Finally, SVMyr confirms 96% of the UniProt set of the electronically annotated myristoylated proteins (31,048) and identifies putative myristoylomes in eight different proteomes, highlighting also new putative NMT substrates. SVMyr is freely available through a user-friendly web server at https://busca.biocomp.unibo.it/lipipred.

Keywords: lipidation; position specific scoring matrix; post-translational modification; protein myristoylation; support vector machines.